Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition.

Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth-immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth-immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth-immunity cross-talk.

Housing helpful invaders: the evolutionary and molecular architecture underlying plant root-mutualist microbe interactions.

Plant root rhizosphere interactions with mutualistic microbes are diverse and numerous, having evolved over time in response to selective pressures on plants to attain anchorage and nutrients. These relationships can be considered to be formed through a combination of architectural connections: molecular architecture interactions that control root-microbe perception and regulate the balance between host and symbiont and developmental architecture interactions that enable the microbes to be 'housed' in the root and enable the exchange of compounds. Recent findings that help to understand the common architecture that exists between nodulation and mycorrhizal interactions, and how this architecture could be re-tuned to develop new symbioses, are discussed here.

Correlation between VITOM(®) videocolposcopy and histopathology for pathognomonic grading criteria.

OBJECTIVE: "Every colposcopic criterion must be mirrored by histopathology". We investigated the histomorphologic equivalent of four colposcopic criteria, which are associated with CIN 2 and/or CIN 3 and therefore called pathognomonic. PATIENTS AND METHODS: We diagnosed inner border sign, ridge sign, rag sign and/or cuffed gland openings using VITOM(®) videocolposcopy in 255 patients which are consistent with major change. Histopathologic examination included immunohistochemical staining for p16, Ki 67 and stathmin-1 and micro-photographic documentation. RESULTS: The histopathologic pattern specific for each of the four pathognomonic colposcopic criteria was reproducibly identified: inner border sign showed a sharp demarcation between low- and high-grade CIN, in ridge sign high-grade CIN adjoined directly the squamocolumnar junction, in rag sign, high-grade CIN was detached from stroma, and in cuffed gland openings, the entrance to a gland was rimmed by CIN, respectively. In 255 patients, the leading pathognomonic sign was inner border in 12.1 %, ridge in 34.1 %, rag in 18 %, and cuffed glands in 35.7 %, respectively. Inner border sign, ridge sign, rag sign and/or cuffed gland openings were associated with CIN 2 or 3 in 97, 98, 98 and 98 %, respectively. In 153 out of 255 patients, we found a combination of pathognomonic signs with ridge sign being the most frequent combined criterion (in 21 % of patients as second pathognomonic sign). CONCLUSION: The morphology of the four pathognomonic colposcopic criteria, inner border sign, ridge sign, rag sign and cuffed crypt openings, is reproduced in histopathology. These criteria are highly associated with CIN 2 or CIN 3.

[Rudolf Schindler and the gastroscopy]. / Rudolf Schindler und die Gastroskopie.

Rudolf Schindler (1888 - 1968) accelerated the spread of gastroscopy in various ways. Together with the technical expert Georg Wolf he developed in 1932 the semiflexible gastroscope, which for about 25 years was the standard gastroscope worldwide before the onset of the fiberscopic era. With his previously constructed rigid gastroscope he became the founder of routine gastroscopy. His Lehrbuch und Atlas der Gastroskopie made him the leading endoscopic authority. He founded the ambulant gastroenterological-endoscopic practice. He was the first to describe and differentiate gastritis. In 1941 he founded the American Gastroscopic Club, he was its first president and the first editor of the journal of this society. For about 40 years he practiced gastroscopy every day with his wife Gabriele. Last but not least, Schindler was a leading authority, which attracted a steadily increasing number of pupils. Schindler was born and grew up in Berlin. He made most of his innovations in Munich between 1920 and 1934. An arrest by the Nazis of two months duration in 1934 drove him away from Germany. In the next decade he made Chicago the Mekka of gastroscopy. In 1943 he moved to California, From 1958 through to 1950 he worked in Belo Horizonte, Brasil. He spent his last years again in Munich. Schindler, possibly the best known digestive endoscopist and an innovative artistical personality, received worldwide high acceptance.

Are modern voice prostheses better? A lifetime comparison of 749 voice prostheses.

The aim of the study was to compare device life of more recent indwelling voice prostheses Provox Vega and Blom-Singer Dual Valve to device life of well-known standard devices (Provox 2, Blom-Singer Classic). In a prospective, non-randomised study, device life of Blom-Singer Classic, Blom-Singer Dual Valve, Provox2, Provox Vega and Provox ActiValve voice prostheses was recorded in a group of 102 laryngectomised patients. In total 749 voice prosthesis were included. Average overall life time was 108 days, median 74 days. The prosthesis with the longest dwell time was the Provox ActiValve (median 291 days). Provox Vega had longer device life compared with Provox2 (median 92 days vs 66 days; p = 0.006) and compared with Blom-Singer Classic (median 92 days vs 69 days; p = 0.004). In conclusion, device lifetimes of Provox Vega and ActiValve were better than those of Provox2 and the Blom-Singer Classic. New voice prostheses, with a defined valve opening pressure (Provox Vega, Provox ActiValve, Blom-Singer Dual Valve) had longer lifetimes than prostheses without a defined opening pressure (Blom-Singer Classic and Provox 2).

The potential impact of biomarker-guided triage decisions for patients with urinary tract infections.

OBJECTIVES: Current guidelines provide limited evidence as to which patients with urinary tract infection (UTI) require hospitalisation. We evaluated the currently used triage routine and tested whether a set of criteria including biomarkers like proadrenomedullin (proADM) and urea have the potential to improve triage decisions. METHODS: Consecutive adults with UTI presenting to our emergency department (ED) were recruited and followed for 30 days. We defined three virtual triage algorithms, which included either guideline-based clinical criteria, optimised admission proADM or urea levels in addition to a set of clinical criteria. We compared actual treatment sites and observed adverse events based on the physician judgment with the proportion of patients assigned to treatment sites according to the three virtual algorithms. Adverse outcome was defined as transfer to the intensive care unit (ICU), death, recurrence of UTI or rehospitalisation for any reason. RESULTS: We recruited 127 patients (age 61.8 ± 20.8 years; 73.2 % females) and analysed the data of 123 patients with a final diagnosis of UTI. Of these 123 patients, 27 (22.0 %) were treated as outpatients. Virtual triage based only on clinical signs would have treated only 22 (17.9 %) patients as outpatients, with higher proportions of outpatients equally in both biomarker groups (29.3 %; p = 0.02). There were no significant differences in adverse events between outpatients according to the clinical (4.5 %), proADM (2.8 %) or urea groups (2.8 %). The mean length of stay was 6.6 days, including 2.2 days after reaching medical stability. CONCLUSIONS: Adding biomarkers to clinical criteria has the potential to improve risk-based triage without impairing safety. Current rates of admission and length of stay could be shortened in patients with UTI.

Chain-length dependent growth dynamics of n-alkanes on silica investigated by energy-dispersive x-ray reflectivity in situ and in real-time.

We compare the growth dynamics of the three n-alkanes C(36)H(74), C(40)H(82), and C(44)H(90) on SiO(2) using real-time and in situ energy-dispersive x-ray reflectivity. All molecules investigated align in an upright-standing orientation on the substrate and exhibit a transition from layer-by-layer growth to island growth after about 4 monolayers under the conditions employed. Simultaneous fits of the reflected intensity at five distinct points in reciprocal space show that films formed by longer n-alkanes roughen faster during growth. This behavior can be explained by a chain-length dependent height of the Ehrlich-Schwoebel barrier. Further x-ray diffraction measurements after growth indicate that films consisting of longer n-alkanes also incorporate more lying-down molecules in the top region. While the results reveal behavior typical for chain-like molecules, the findings can also be useful for the optimization of organic field effect transistors where smooth interlayers of n-alkanes without coexistence of two or more molecular orientations are required.

[Logistic requirements and biopsy of periprosthetic infections: what should be taken into consideration?]. / Logistische Voraussetzungen und Probenentnahme bei periprothetischen Infektionen: Was muss beachtet werden?

Preoperative diagnosis of periprosthetic infections is particularly important before revision of knee and hip arthroplasties because of the therapeutic consequences. Therefore, periprosthetic infections should be ruled out before any revision surgery is performed. Of the different diagnostic methods direct techniques which allow the direct detection of microorganisms with testing of antibiotic sensitivity are recommended. This allows microorganism-specific systemic and local antibiotic therapies and helps to reduce the risk of development of resistance. In our studies it could be shown that the time for incubation to detect microorganisms should be 14 days and that biopsy of periprosthetic tissues is superior to aspiration alone because it combines several diagnostic methods (microbiological and histological). It is preferable to repeating an aspiration when data are unclear, i.e. in cases of potentially false positives or negatives results of aspiration.

Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production.

Interleukin (IL)-1 is a proinflammatory cytokine with pleiotropic effects in inflammation. IL-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (MAP) kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, as well as transcription factor nuclear factor kappaB (NF-kappaB). IL-1 signaling results in cellular responses through induction of inflammatory gene products such as IL-6. One of the earliest events in IL-1 signaling is the rapid interaction of IL-1 receptor-associated kinases, IRAK and IRAK-2, with the receptor complex. The relative roles of IRAK and IRAK-2 in IL-1 signaling pathways and subsequent cellular responses have not been previously determined. To evaluate the importance of IRAK in IL-1 signaling, IRAK-deficient mouse fibroblast cells were prepared and studied. Here we report that IL-1-mediated activation of JNK, p38, and NF-kappaB were all reduced in embryonic fibroblasts deficient in IRAK expression. In addition, IL-6 production in response to IL-1 was also dramatically reduced in IRAK-deficient embryonic fibroblasts and in skin fibroblasts prepared from IRAK-deficient mice. Our results demonstrate that IRAK plays an essential proximal role in coordinating multiple IL-1 signaling pathways for optimal induction of cellular responses.

Centrioles of a human cancer: intercellular order and intracellular disorder.

A continuous, symmetric, and periodic pattern of long-range spatial order has been observed among the centrioles of both normal and neoplastic cells. Consecutive ultrathin sections of lethal human esophageal cancers have revealed a defect in the centriolar angle with random angularity and random, long, intercentriolar distances.

Electron probe x-ray microanalysis of a normal centriole.

A scanning spectrometer with lithium fluoride, ammonium dihydrogen phosphate, and gypsum crystals was used to detect the x-ray spectrum of a normal centriole, the transmitted electron image of which was used to focus the exciting electron beam to the size, shape, and position of the centriole in a 700-angstrom section of intact tissue.

A novel 3D printed radial collimator for x-ray diffraction.

We demonstrate the use of a 3D printed radial collimator in X-ray powder diffraction and surface sensitive grazing incidence X-ray diffraction. We find a significant improvement in the overall signal to background ratio of up to 100 and a suppression of more than a factor 3 · 105 for undesirable Bragg reflections generated by the X-ray "transparent" windows of the sample environment. The background reduction and the removal of the high intensity signals from the windows, which limit the detector's dynamic range, enable significantly higher sensitivity in experiments within sample environments such as vacuum chambers and gas- or liquid-cells. Details of the additively manufactured steel collimator geometry, alignment strategies using X-ray fluorescence, and data analysis are also briefly discussed. The flexibility and affordability of 3D prints enable designs optimized for specific detectors and sample environments, without compromising the degrees of freedom of the diffractometer.

Induction of ouabain-resistant mutation and sister chromatid exchanges in Chinese hamster cells with chemical carcinogens mediated by human pulmonary macrophages.

Pulmonary macrophages (PAM) metabolically activated benzo[a]pyrene [B(a)P] and its proximate carcinogenic metabolite, (+/-)trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol), to ultimate mutagens that were detected in cocultivated Chinese hamster V79 cells. Increases in the frequency of ouabainresistant (O(r)) mutations and sister chromatid exchanges were found in V79 cells only when they were cocultivated with both PAM and the chemical procarcinogens. 7,8-Diol caused higher frequencies of both O(r) mutations and sister chromatid exchanges than did the parent compound, B(a)P. When metabolically activated by PAM the mean O(r) mutation frequency caused by B(a)P was 9 O(r) mutants/10(6) surviving V79 cells per 10(6) PAM and a 10-fold interindividual variation (range, 2-21) was found. The mean O(r) mutation frequency caused by 7,8-diol was 64 and a ninefold interindividual variation (range, 14-120) was found. In the absence of PAM, the O(r) mutation frequency in V79 cells was one or less O(r) mutant per 10(6) survivors. 7,8-Benzoflavone, an inhibitor of mixed function oxidases, reduced the frequencies of O(r) mutations and of sister chromatid exchanges in V79 cells caused by 7,8-diol and B(a)P. As expected 7,8-benzoflavone did not influence the frequency of O(r) mutations caused by one of the ultimate mutagens derived from B(a)P and 7,8-diol, (+/-)7beta, 8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. These data are consistant with the hypothesis that PAM may play a role in the activation of environmental chemical procarcinogens.

Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patients.

Coating a silica surface with the isolated lipoprotein receptor proteoheparan sulfate (HS-PG) from arterial endothelium and vascular matrices and adding both the atherogenic VLDL/IDL/LDL lipid fraction in its native composition and Ca(2+) ions, we could observe in vitro the earliest stages of atherosclerotic plaque development by ellipsometric techniques (patent EP 0 946 876). This so-called nanoplaque formation is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies on statins in cardiovascular high-risk patients. In eight patients who had undergone an aortocoronary bypass operation, the reduction of atherosclerotic nanoplaque formation amounted to 11.9+/-2.5% (p<0.0078) and of nanoplaque size to 24.4+/-8.1% (p<0.0234), respectively, after a 2-month therapy with Ginkgo biloba extract (2x 120 mg daily, EGb 761). Additionally, superoxide dismutase (SOD) activity was upregulated by 15.7+/-7.0% (p<0.0391), the quotient oxLDL/LDL lowered by 17.0+/-5.5% (p<0.0234) and lipoprotein(a) concentration decreased by 23.4+/-7.9% (p<0.0234) in the patients' blood. The concentration of the vasodilating substances cAMP and cGMP was augmented by 37.5+/-9.1% (p<0.0078) and 27.7+/-8.3% (p<0.0156), respectively. A multiple regression analysis between the patients' VLDL/IDL/LDL lipoprotein fraction applied in the ellipsometry measurements as well as the further risk factors oxLDL/LDL and Lp(a) on the one hand and changes in nanoplaque formation on the other hand reveals a basis for a mechanistic explanation of nanoplaque reduction under ginkgo treatment. The atherosclerosis inhibiting effect is possibly due to an upregulation in the body's own radical scavenging enzymes and an attenuation of the risk factors oxLDL/LDL and Lp(a).

Increased risk of acute myeloid leukaemia after treatment for breast cancer.

This study evaluates the risk of acute myeloid leukaemia (AML) in patients treated for breast cancer. We included all 6360 breast cancer patients that were recorded at the Geneva Cancer Registry between 1970 and 1999. Patients were followed for AML occurrence until December 2000. We calculated standardized incidence ratios of AML and identified factors modifying the risk of AML by multivariate Cox analysis. Twelve (0.2%) patients developed AML. In general, patients treated for breast cancer had a 3.5-fold (95% confidence interval (CI): 1.8-6.0) increased risk of developing AML compared with the general population. In particular, patients who were older than 70 years at breast cancer diagnosis and those treated with radiotherapy (with or without chemotherapy) had a significantly increased risk of developing AML. This population-based study confirms that radiotherapy increases the risk of AML. Due to the relatively low number of women treated with chemotherapy without radiotherapy and due to the infrequency of the disease, the question of whether chemotherapy alone increases this risk of AML cannot yet be answered.

Metabolism of acyclic and cyclic N-nitrosamines in cultured human bronchi.

The metabolism of carcinogenic N-nitrosamines was studied in normal-appearing bronchial specimens obtained from 4 patients. Explants of bronchi were cultured in a chemically defined medium for 7 days. N-Nitrosamines [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine (DEN), N,N'-dinitrosopiperazine (DNP), N-nitrosopyrrolidine (NPy), and N-nitrosopiperidine (NPd)] labeled with 14C were each then added at 100 mumoles for 24 hours. Measurable CO2 was formed by bronchial explants from: 1) DMN, DEN, and NPy in all 4 patients; 2) DNP in 3 of 4 patients; and 3) NPd in only 1 of 4 patients. In all bronchial specimens, these N-nitrosamines and/or their metabolites bound to bronchial mucosal DNA and protein. Binding levels were higher to protein than to DNA. Binding levels of DNP were as high as those with the two acyclic N-nitrosamines DMN and DEN, but binding levels of NPy and NPd were lower. Human bronchus was shown to metabolize and bind acyclic and cyclic N-nitrosamines found in the environment and in tobacco smoke.

Metabolism of dimethylnitrosamine and 1,2-dimethylhydrazine in cultured human bronchi.

The metabolic activation of several chemical classes of procarcinogens is being studied in cultured human bronchi. Previous studies have shown that carcinogenic polynuclear aromatic hydrocarbons are metabolically activated by the bronchial epithelium. In the study reported here, dimethylnitrosamine and 1,2-dimethylhydrazine were also found to bind to both cellular DNA and protein. Bronchial DNA was methylated in both the O-6 and N-7 positions of guanine. In addition to polynuclear aromatic hydrocarbons, an aliphatic nitrosamine and a methylhydrazine can now be added to the list of xenobiotic chemical carcinogens metabolized by human bronchus.

Cervical Strip Biopsy for High-Grade Cervical Intraepithelial Lesions: a Valid Alternative to Conventional Punch Technique.

Introduction: To evaluate, if targeted strip biopsies decrease trauma/pain perception while maintaining diagnostic accuracy in patients with the diagnosis of high-grade squamous intraepithelial lesions of the uterine cervix. Patients and Methods: Between July 1st and December 31st 2014 we performed colposcopically directed strip biopsies in 102 patients with colposcopic suspicion of high-grade squamous intraepithelial lesions of the uterine cervix. We used a 3 mm curette for harvesting tissue samples under VITOM® videocolposcopy. So far, 60 patients underwent additional loop excision. Histologic examination of strip biopsies and loop specimens included routine hematoxylin and eosin staining as well as immunohistochemical staining for p16, Ki 67 and stathmin-1. Results: 55 patients (53 %), were histologically diagnosed with cervical intraepithelial neoplasia grade 3 on strip biopsies. Adenocarcinoma in situ was diagnosed in 2 patients (2 %), cervical intraepithelial neoplasia grade 2 in 35 patients (34 %), and cervical intraepithelial neoplasia grade 1 in 10 patients (10 %). The agreement between histologic results of strip biopsy and loop specimen was highly significant: In all 60 strip biopsies diagnosed with high-grade squamous intraepithelial lesions this diagnosis was confirmed histologically during follow-up loop specimen excision (high-grade squamous intraepithelial lesions in 58 patients, invasive disease in 2 patients). The pain level experienced during strip biopsy was rated on average 0.25 on a scale from 0 to 10. No clinically significant bleeding was reported. Conclusion: Targeted strip biopsies with a 3 mm curette are a reliable procedure to diagnose high-grade squamous intraepithelial lesions of the uterine cervix and yield high patient satisfaction (Video 1).

Antibodies to chlamydial lipopolysaccharides in unstable angina pectoris.

Patients with coronary artery disease frequently have elevated antibody titers against Chlamydia pneumoniae, but whether antichlamydial antibody titers are correlated with prognosis in unstable angina remains unclear. We therefore investigated the sera of 1,096 patients with unstable angina regarding immunoglobulin (Ig) IgG, IgA, and IgM antibody titers against chlamydial lipopolysaccharides (LPS) and the concentrations of C-reactive protein (CRP) and troponin T (TnT). Anti-LPS IgG titers were increased in 45% of patients at enrollment and in 48% of patients at discharge (p <0.0001). Anti-LPS IgA titers were increased in 27% of patients at enrollment and in 33% of patients at discharge (p <0.0001). Patients who subsequently died had significantly lower IgM titers at enrollment than patients without events (p = 0.016). IgG, IgA, or IgM titers did not correlate with concentrations of CRP or TnT. In this large-scale study of patients with unstable angina, we frequently found elevated antichlamydial antibody titers. Patients with low IgM anti-LPS titers were at risk for subsequent death. However, there was no correlation between antichlamydial antibody titers and CRP or TnT.